Dissertation > Excellent graduate degree dissertation topics show

The Applied Basic Research of Bone Marrow Mononuclear Cells Autologous Transplantation into Infarcted Myocardium in Dogs

Author: DengXueFeng
Tutor: GaoChangQing
School: PLA Postgraduate Medical School
Course: Surgery
Keywords: myocardial infarction (MI) bone marrow mononuclear cells (BM-MNCs) myocardial contrast echocardiography (MCE) magnetic resonance imaging (MRI) Superparamagnetic iron oxide nanoparticles (SPIO)
CLC: R542.22
Type: PhD thesis
Year: 2008
Downloads: 90
Quote: 0
Read: Download Dissertation

Abstract


Objectives: 1. To establish myocardial infarction (MI) model in dog and noninvasive evaluation the size of MI by myocardial contrast echocardiography (MCE) and contrast-enhanced magnetic resonance imaging (MRI) then to compare with histological standards. 2. To study the role of improvement of post-MI LV function and myocardial blood flow by autologous bone marrow mononuclear cells (BM-MNCs) transplantation in canine models. 3. To explore the method of tracking magnetically labeled BM-MNCs in vivo in a canine model.Methods: 1. To induce a MI, twenty male adult dogs were intubated and ventilated. After left sided thoracotomy, left anterior descending coronary artery were occluded by a permanent ligation. Two weeks later, the size of MI was measured by MCE and enhanced-MRI among four MI model dogs, which was compared with postmortem size of fibrosing scar. 2. Fourteen canine MI models were randomized into three groups. After two weeks post-MI, groupl received 10~7 BM-MNCs via epicardium, group2 received 10~5 BM-MNCs by the same way and group3 as controls was injected identical quantitative phosphate buffered saline (PBS). Four weeks after BM-MNCs or PBS injection, all the animals underwent transthoracic echocardiography and MCE. Finally, the hearts were excised and then calculated microvascular density by HE staining. 3. Feridex is one FDA-approved SPIO nanoparticle and shows hypointense T2 signal on MRI. Autologous BM-MNCs were labeled by Feridex in vitro, and then were injected into MI regions on four models. To assess Feridex labeled BM-MNCs, animals were imaged at one, two and four weeks after cell injection by 1.5T MRI. Scan parameters for ECG gated, free-breathing navigator and three dimensional steady state free precession (3DSSFP ) were optimized to detect the cells. After humane euthanasia, the hearts were excised and sliced along short-axis plane. Histology corresponding to MRI slices was performed.Results: 1. The MI incidence and the mortality was 90% and 10% respectively. The MI size measured by MCE, enhanced-MRI and postmortem analysis was 2. 29±0. 50cm~2、1. 73±0. 72 cm~2 and 1. 70±0. 85 cm~2 respectively. There were significant differences (p<0.05). Viable myocardium around MI was all detected accurately by MCE and enhanced-MRI. 2. After BM-MNCs injection 4 weeks, LVEF (62%, 58% vs 48%) and E/A value (0.78, 0.89 vs 0.42) both improved significantly (p<0.05). The size of MI decreased from2.74cm~2 to 1.91 cm~2 in group 1 and from 2.49cm~2 to 2.03 cm~2 in group2 and there were significant differences (p<0.05). Mi-thickness showed no differences among the three groups (p>0.05). The A、K and A×K values measured by MCE were significantly higher than those in pre-injection of BM-MNCs (p<0.05), but no changes in control group (p>0.05). 3. Prussian blue staining revealed more than 98% of BM-MNCs were labeled by Feridex and BM-MNCs appeared to be unaffected by magnetically labeling. Three dogs injected Feridex- BM-MNCs were visualized at one week by MRI, but none of unlabeled BM-MNCs were seen. All lesions that were detected within one week could not be visualized over four week. The dot injected Feridex-cells which fixated by 4 % methanal also was seen at one week by MRI, but the signal disappeared at two week. DE-MRI confirmed the presence of Feridex-BM-MNCs injection within the infarcted myocardium. 4. A large amount of neovascularization appeared in BM-MNCs injection dogs under light microscope. The mean microvascular density in three groups was 79.8±4.8/mm2, 74.8±6.5/mm~2 and 28.6±5.2/ mm~2 respectively (p<0.05). By Prussian blue staining, differentiation into vascular endothelial cell and cardiocyte-like cells could be found under light microscope and Feridex could be englobed by macrophages.Conclusions: 1. The method of establishing canine MI model by ligating LAD and branches after thoracotomy is reliable and preferred. MCE and enhanced-MRI can accurately detect and assess MI and viable myocardium. 2. Autologous BM-MNCs engrafts via epicardium improve cardiac function and myocardial blood flow of post-MI on canine models. 3. The sites of injection of Feridex-BM-MNCs can be detected by clinical 1.5T MR. Pathological microscopic pictures show that BM-MNCs can differentiate into cardiocyte-like cells and vascular endothelial cell. 4. MCE and MRI technology can be applied to clinical researches about stem cells as noninvasive methods.

Related Dissertations

  1. The Application of STIR-FLAIR and T2W-SPIR for Diagnosing the Orbital Lesions: a Contrast Study,R777
  2. Application of Functional MR Imaging in Diagnose for Prostate Cancer,R737.25
  3. Clinical Effects, Imaging Study and Treatment of TOT Procedure Combined with Modified Pelvic Floor Reconstruction on Female Stress Urinary Incontinence,R699.7
  4. Comparison between MRI Performance of Cervical Disc Injury with Intraoperative Cervical Discography in Lower Cervical Spine with Fracture and Dislocation,R687.3
  5. The High-Resolution Microscopy Coil MRI for Orbit: Preliminary Study,R445.2
  6. MR Imaging of Cruciate Ligament and/or Meniscal Tears,R445.2
  7. In Vivo MR Tracking of Transplanted Spio-labeled Bone Marrow Stem Cells in Vitro and Stransplantation for Treating Traumaic Brain Injury in Rat,R445.2
  8. The Study of Evaluating Relevance of Characteristic of Coronary Plaque and the ACS by 64-slice Spiral CT,R541.4
  9. The Clinical Study of Assessment of Left Ventricular Function in Patients with Successful Coronary Revascularization by Doppler Tissue Imaging,R540.4
  10. The Change of Bone Marrow-derived Stem Cells (BMSC) in Peripheral Blood of Patients with Acute Myocardial Infarction and Its Clinical Significance,R542.22
  11. On high-density lipoprotein and triglycerides in molecular genetics,R363
  12. Intravenous Myocardial Contrast Echocardiography with Self-made Acoustic Contrast Agent,R445.1
  13. Experimental Study of Optimizing Mechanical Index for Three Ultrasonic Contrast Agents and Quantifying Myocardial Perfusion with Contrast Echocardiography,R445.1
  14. Study of Relation between Myocardial Infarction and the Autonomic Nervous System,R542.22
  15. Visualization of pulse access to information and applications of the technology and Comparative Study,R319
  16. Feasibility Study of Navigator-Gated 3D Delayed-Enhancement and 2D DIR FSE Black-Blood Cardiac MRI,R445.2
  17. 1. In Vivo Imaging of Bone Marrow Mesenchymal Stem Cells Transplanted into Myocardium Using Magnetic Resonance Imaging: A Novel Method to Trace the Transplanted Cells 2. Retention, Distribution, Migration of the Bone Marrow Mesenchymal Stem Cells after Tr,R542.22
  18. The midfoot bone and joint sectional anatomy and MRI contrast study,R445.2
  19. Expression of Aquaporin-4 (AQP-4) and Its Effect on Permeability of Blood-brain Barrier during Traumatic Brain Injury in Rats,R651.15
  20. Synthesis and Property Investigation of Functionlized Magnetic Nanoparticles,TB383.1

CLC: > Medicine, health > Internal Medicine > Heart, blood vessels ( circulatory ) disease > Heart disease > Myocardial diseases > Myocardial infarction
© 2012 www.DissertationTopic.Net  Mobile